Lupus nephritis (LN) occurs in majority of patients with systemic lupus erythematosus (SLE) and represents a major source of morbidity and mortality. Recent genome wide association studies (GWAS) of patients with SLE identified mutations in NF-?B signaling components, including A20-binding inhibitor of NF-?B 1 (ABIN1), a polyubiquitin binding protein which inhibits NF-?B activity. Preliminary findings from other study show that 2 SNPs in the ABIN1 gene (rs7708392 and rs4958881) have a strong association with LN in European-Ancestry and African American SLE patients, respectively. We have found that immortalized B cells from patients with rs4958881 have elevated levels of toll-like receptor-mediated cytokine/chemokine production as compared to wild type. We show that the ABIN1 [D485N] knock-in mice develop progressive renal function impairment and glomerulonephritis with histologic features of the most common and severe class III/IV human LN.Our results suggest that ABIN1 polymorphisms and subsequent dysfunction contributes to the pathogenesis of LN.

Role of abin 1 mutation in lupus nephritis

245th National Meeting (2013)

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